Method and device for predicting the fertile phase of women

ABSTRACT

A method and device to predict ovulation in a female human by measuring changes in the concentration of a number of ions in eccrine sweat is disclosed. The concentration, or changes in concentration, of one or more ions are determined throughout the day and analyzed against predetermined patterns in order to predict ovulation one to five days in advance. This permits the user to more accurately determine commencement of the fertile phase, which for female humans is generally considered to be about four days prior to ovulation to one day after ovulation. The concentration of the ions measured include sodium (Na+), potassium (K+), ammonium (NH 4 +), calcium (Ca 2 +), chloride (Cl−) and nitrate (NO 3 −) To further increase the accuracy of the reading, a large number of readings can be obtained throughout a day and statistically analyzed to determine the change over time. In addition, the concentration of two or more ions can be obtained to increase accuracy. Ratiometric measurements between two or more ions can be determined to increase accuracy and account for ion accumulation on the skin. Ratiometric measurements between ammonium (NH 4 +) and calcium (Ca 2 +) have been found to provide more distinct patterns because the concentrations of these two ions change in opposite directions during the relevant period preceding ovulation.

FIELD OF THE INVENTION

[0001] The present invention relates to a method and apparatus fordetermining fertility status of a female. More specifically, theinvention relates to a method and apparatus for predicting ovulation andthereby determining the fertile phase from the non-fertile phase in thereproductive cycle of a female mammal, and preferably a female human.

BACKGROUND OF THE INVENTION

[0002] The fertile phase in a mammal can be defined as the period duringwhich sperm present in the uterus may encounter and fertilize an egg.Generally, in female humans, the average reproductive cycle is 28 days,of which a released egg survives only about 12 to 24 hours. However, theuterus is capable of storing sperm for a period of up to four days.Thus, the fertile phase can commence up to four days prior to ovulationand last for up to one day after ovulation. But, the time periodfollowing ovulation, when an egg is released, is relatively narrow.

[0003] Many prior art devices have been proposed to determine whenovulation has occurred. However, by merely determining when ovulationhas occurred, these prior art devices and methods only determine afraction of the fertile phase in a female human. Clearly, an advantagecan be obtained by predicting ovulation at least four days in advance,which will encompass the entire fertile phase of a woman. In this way,pregnancy can be planned.

[0004] Several methods for determining ovulation have been proposed inthe past. In female humans, the maturation of ovarian follicles whichwill eventually release a fertile egg are effected by the action ofFollicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) secretedby the anterior lobe of the pituitary. The ovulatory phase of themenstrual cycle is preceded by a significant rise in serum totalestrogens 24 to 48 hours prior to ovulation, which prepare the uterusfor possible implantation. The rise in estrogens is followed by a rapidrise in serum luteinizing hormone (LH) reaching a peak 12 to 24 hoursprior to ovulation. Many other physiological conditions also changearound the time of ovulation. For instance, basal body temperature (BBT)reaches a nadir followed by a sharp rise around the time of ovulation.Cervical mucus undergoes viscosity changes stimulated by rising estrogenwhich can help direct sperm towards the egg.

[0005] Several fertility detectors have been developed which measurethese various hormones or their indirect physiological effects. The BBTmethod, referred to above, generally requires female humans to taketheir vaginal temperature and chart the value every morning beforerising. Besides the considerable diligence involved, the method isgenerally only accurate within one to two days of ovulation, and givesno prior notice. Cervical mucus measurements have been regarded assomewhat more helpful. Women can examine their cervical mucus for athinning of the mucus just before ovulation, which allows it to be drawnintact between the fingers and is referred to as the spinbarkeitreaction. Another method involves examining the cervical mucus under amicroscope and looking for a “ferning” reaction indicative of imminentovulation. A further method measures vaginal mucus conductivity usingimpedance probes which allows a somewhat more quantitative estimation ofthe mucus changes as disclosed in U.S. Pat. No. 4,770,186. U.S. Pat. No.5,209,238 to Sundhar discloses an ovulation monitor which determines thepresence of a viable egg by sensing the mucous density, basil bodytemperature, and pH level and LH level of secretion in the vagina.

[0006] However, these prior art methods suffer from the disadvantagethat they determine ovulation, but do not provide a means for predictingovulation, thereby missing a large portion of the fertile phase. Also,cervical mucus examination suffers from subjective errors as well asbeing arduous and again gives little to no prior notice of ovulation.

[0007] U.S. Pat. No. 5,685,319 to Marett discloses that a significant pHnadir in female eccrine sweat was found to occur approximately five tosix days prior to ovulation. In this way, tracking the pH of eccrinesweat could assist in predicting ovulation, and thereby determining thefertility status of a female human. Furthermore, an advantage oftracking pH is that it is inherently buffered in that the hydrogen ionsH⁺ can react with the hydroxide ion (OH) to form water. In addition,even though there is no satisfactory mechanism to explain skin acidity,previous studies have found that eccrine sweat of women is alsogenerally buffered by either the lactic acid/lactate system, free aminoacid secretion or CO₂ bicarbonate. The benefit of having the pH bufferedis that changes in the quantity of eccrine sweat, such as throughevaporation or increased physical activity, will not greatly affect thepH, thereby avoiding spurious readings.

[0008] Several researchers have also investigated changes of other ionsin eccrine sweat. For instance, Lieberman and Taylor looked at chloride(Cl−), sodium (Na+) and potassium (K+) in the eccrine sweat of femalehumans (Lieberman et al. JAMA Feb. 21, 1996, Vol. 195, No. 8, pages117-123 and Taylor et al., Journal of Investigative Dermatology, Vol.53, No. 3, pages 234-237, 1969). However, neither Lieberman nor Taylorinvestigated changes in the concentrations of these ions prior toovulation and for the purpose of predicting ovulation.

[0009] One disadvantage of much of the prior art has been that it failsto predict ovulation at least three to six days in advance. Because ofthis, the prior art methods and devices fail to determine the entirefertile phase of a female.

[0010] Furthermore, other than for measuring pH, the prior art hasfailed to consider what other characteristics of eccrine sweat of femalehumans can be used to predict ovulation. The prior art has failed toprovide a reliable and consistent method and device to obtainmeasurements of the characteristics of eccrine sweat, such as changes inthe concentrations of ions, other than pH. In addition, the prior arthas failed to provide a method and device which can measure changes inconcentrations of ions in eccrine sweat which are not naturallybuffered, as is pH, and which may therefore vary due to other factors,such as eccrine sweat volume due to increased physical activity, ambienttemperature or evaporation.

[0011] Accordingly, there is a need in the art for a method and deviceto reliably and economically predict ovulation three to six days inadvance in order to determine a larger portion of the fertile phase of afemale mammal, and preferably a female human. There is also a need for amethod and device to predict ovulation which is easy to use, reliableand inexpensive.

SUMMARY OF THE INVENTION

[0012] Accordingly, it is an object of this invention to at leastpartially overcome some of the disadvantages of the prior art. Also, itis an object of this invention to provide an improved method and deviceto assist in predicting ovulation in female mammals, and preferablyfemale humans, about one to six days in advance, which is reliable andcan be economically implemented.

[0013] Accordingly, in one of its aspects, this invention resides in adevice for determining a fertile phase of a female human comprising: (a)a sensor for sensing concentrations of at least two ions in the eccrinesweat of the female and generating output signals indicative ofconcentrations of the at least two ions in the eccrine sweat; (b) aprocessor for controlling the sensor to sense the concentrations of atleast two ions in the eccrine sweat substantially simultaneously and atleast on a daily basis; and wherein the processor monitors the outputsignals from the sensor to identify a distinct change in theconcentration of one of the at least two ions following an inversionwhich indicates the female human is in the fertile phase.

[0014] In a further aspect, the present invention resides in a devicefor determining the fertility status of a female mammal comprising: (a)a sensing means for sensing at least one ion selected from the groupconsisting of potassium (K+), ammonium (NH₄+), calcium (Ca₂+), chloride(Cl−), nitrate (NO₃) and sodium (Na+), in the eccrine sweat of thefemale mammal and generating output signals indicative of theconcentration of ions in the eccrine sweat; (b) processor means forcontrolling the sensing means to sense the at least one ion in theeccrine sweat at least on a daily basis; and wherein the processor meansmonitors the output signals stored in the storage means to identify adistinct change in a concentration of one of the ions following aninversion which indicates the female mammal is in the fertile phase.

[0015] One advantage of the present invention is that changes inconcentrations of several different types of ions in eccrine sweat canbe sensed and analyzed to predict ovulation in female mammals. Theseions include sodium (Na+), potassium (K+), ammonium (NH₄+), calcium(Ca₂+) and nitrate (NO₃−). In this way, different types of sensors canbe selected to sense the corresponding ions, such as sodium (Na+),chloride (Cl−), ammonium (NH₄+), potassium (K+), calcium (Ca₂+) andnitrate (NO₃−). In addition, sensors to sense the conductivity ofeccrine sweat, thereby indirectly measuring the total concentration ofall of the ions, can be used. This permits a selection to be made as towhich sensor is most reliable for a particular situation.

[0016] For instance, in colder climates where the user may excrete lesseccrine sweat, a different type of ion, and a different type of sensor,could be used than in warmer climates where more eccrine sweat isexcreted. Likewise, in veterinarian use, different sensors to sensedifferent ions could be used depending on the particular situation andmammal whose fertility status is being sensed. Furthermore, this permitsthe sensor to be selected based on features other than reliability, suchas cost and availability.

[0017] A further advantage of the present invention is that it providesfor measurement of changes in concentrations of more than one ion ineccrine sweat. In this way, the changes in concentration of two or moreions can be monitored to provide confirmatory readings in order to moreaccurately predict ovulation and avoid false readings due tonon-hormonal effects such as eccrine sweat volume, diet and stress.

[0018] A further advantage of measuring changes in concentration of morethan one ion in eccrine sweat is that ratiometric measurements can beobtained. For example, it has been discovered that sodium (Na+) andchloride (Cl−) ions in eccrine sweat are the dominant ions and can beused to reference the rate of sweating. By using sodium (Na+) orchloride (Cl−) as a reference ion, the concentration changes in otherions in relation to sodium (Na+) and chloride (Cl−) can be assessed. Theratio of chloride (Cl−) to sodium (Na+) is particularly constant, whichis expected because chloride (Cl−) is the main counter ion for sodium(Na+). While the concentrations of chloride (Cl−) and sodium (Na+) ionscan each be measured individually to predict ovulation, these ions canalso be used in order to account for changes in concentrations of theother ions, such as potassium (K+), ammonium (NH₄+), calcium (Ca₂+) andnitrate (NO₃−), due to changes in the quantity of eccrine sweat, such asthrough evaporation, increased ambient temperature, increased physicalactivity or ion accumulation on the skin over time. This is the casebecause while sodium (Na+) and chloride (Cl−) surge prior to ovulation,they do not surge as much as other ions, such as nitrate (NO₃−), calcium(Ca₂+) and ammonium (NH₄+). Accordingly, by performing a ratiometricmeasurement between one of the ions, such as potassium (K+), ammonium(NH₄+), calcium (Ca₂+) or nitrate (NO₃−), with respect to either sodium(Na+) and/or chloride (Cl−), a more consistent measurement of the ionscan be obtained, and changes in concentration due to changes in eccrinesweat volume and ion accumulation on the skin over the day can beaccounted for to some extent. In this way, a more accurate measurementcan be made.

[0019] A still further advantage of the present invention is that someof the ions have been found to have counteracting effects. For instance,the concentration of calcium (Ca₂+) has been found to change in theopposite direction during the time period of interest precedingovulation. In this way, performing a ratiometric measurement of calcium(Ca₂+) with respect to another ion, such as ammonium (NH₄+), can improveprediction because a more pronounced effect will be monitored.

[0020] In order to further improve the prediction, three ions may bemeasured, such as ammonium (NH₄+), calcium (Ca₂+) and either sodium(Na+) or chloride (Cl−). Measurements can then be made with respect toammonium (NH₄+) and sodium (Na+), as well as sodium (Na+) and calcium(Ca₂+), to account for changes in concentrations of all of the ions dueto accumulation on the skin or changes in eccrine sweat volume due totemperature and/or physical activity. These two ratiometric measurementscan then be compared to obtain a ratiometric measurement of ammonium(NH₄+) with respect to calcium (Ca₂+), but with some of the changes dueto other effects accounted for because the concentrations of ammonium(NH₄+) and calcium (Ca₂+) were initially measured with respect to sodium(Na+).

[0021] A further advantage of the present invention relates to oneembodiment where the method is implemented by means of a device that isin contact with the skin for extended periods of time, such as 12 hourson a daily basis. This facilitates taking several readings over thecourse of a day so that a better statistical analysis can be performed.Furthermore, by taking several readings over the course of a day,spurious readings can be identified and eliminated. Furthermore, thedevice can, in a preferred embodiment, sense when it is not on the skinso that a reading will not be taken at this time. This obviouslydecreases the number of incorrect readings, while at the same time, notadversely affecting the overall daily reading, because a large number ofother readings will likely be obtained during the course of the day andcan be used to obtain a reliable average. In other words, by taking alarge number of readings, such as 10 to 48, over a period of time, suchas 24 hours, and statistically examining these readings, changes ineccrine sweat not related to menstrual hormones can be largely removed.

[0022] A still further advantage of the present invention is thatreadings from previous reproductive cycles can be stored for the samefemale. These stored readings can be used to better predict ovulation byignoring readings taken during the early part of the reproductive cycle.For instance, if it is known from previous reproductive cycles that aparticular female human never ovulates within four days of menstruationstarting, the readings at the beginning of the reproductive cycle,following menstruation will be given less weight in predicting ovulationin the future. In a preferred embodiment, the duration of thereproductive cycle is determined and then, for female humans, ovulationis estimated to occur at some time in the last 19 days of thereproductive cycle. This coincides with the Luteal period which isgenerally 14 days from ovulation to menstruation for humans.Accordingly, the portion of the reproductive cycle prior to 19 days fromthe estimated start of menstruation is given less weight or disregardedfor the purposes of determining the fertile phase of the female.

[0023] Further aspects of the invention will become apparent uponreading the following detailed description and drawings which illustratethe invention and the preferred embodiments of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In the drawings, which illustrate embodiments of the invention:

[0025]FIGS. 1A, 1B and 1C are diagrams illustrating changes in theconcentrations of potassium (K+) and sodium (Na+) ions in eccrine sweat,as well as sweat conductivity during one reproductive cycle of a femalehuman, and FIG. 1D is a diagram illustrating changes in theconcentration of potassium (K+) ions in eccrine sweat;

[0026]FIGS. 2A, 2B and 2C are diagrams illustrating the concentration ofchloride (Cl−) ions in eccrine sweat, during one reproductive cycle of afemale human;

[0027]FIGS. 3A to 3E are diagrams showing ratiometric measurements ofammonium (NH₄+), chloride (Cl−), sodium (Na+), potassium (K+) andcalcium (Ca₂+) with respect to sodium (Na+) during one reproductivecycle of a female human;

[0028]FIG. 4 is a diagram showing ratiometric measurement of ammonium(NH₄+) with respect to calcium (Ca₂+) during one reproductive cycle of afemale human;

[0029]FIG. 5 is a diagram showing ratiometric measurement of ammonium(NH₄+) with respect to sodium (Na+) during one reproductive cycle of afemale human;

[0030]FIG. 6 is a diagram showing ratiometric measurement of sodium(Na+) with respect to calcium (Ca₂+) during one reproductive cycle of afemale human;

[0031]FIG. 7 is a diagram showing a relative ratiometric measurementexpressed as potential difference of sodium (Na+) with respect tocalcium (Ca₂+) during one reproductive cycle of a female human;

[0032]FIG. 8 is a diagram showing a relative ratiometric measurementexpressed as potential difference of chloride (Cl−) with respect tocalcium (Ca₂+) during one reproductive cycle of a female human;

[0033]FIG. 9 is a schematic diagram showing a circuit for a devicehaving a sensor for sensing two ions according to one embodiment of theinvention;

[0034]FIGS. 10A, 10B and 10C illustrate electrodes for sensing ammonium(NH₄+), chloride (Cl−) and calcium (Ca₂+), respectively;

[0035]FIG. 11 illustrates a schematic diagram showing a circuit for adevice having a sensor for sensing two ions with respect to a referenceaccording to one embodiment of the invention;

[0036]FIG. 12 is an exploded view of an apparatus which can be strappedto the wrist and used with a microprocessor to effect measurement of theconcentration of ions in the eccrine sweat according to one embodimentof the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0037] The present invention involves a method and device to predictovulation in female mammals, such as the female human, several days inadvance by monitoring changes in eccrine sweat. Ovulation is preferablypredicted in advance by at least one half of the time period that spermis capable of surviving within the female mammal so that a largerportion of the fertile phase can be determined. In this way, the presentinvention provides a reliable self-monitoring personal use test topermit determination of substantially the entire fertile phase of thefemale. It can also be used by a physician in the treatment of femaleinfertility since many diagnostic or therapeutic measures depend on theaccurate prediction and detection of ovulation.

[0038] Eccrine sweat is a thin watery fluid which is secreted onto thesurface of skin by the eccrine sweat glands. Generally, thick skin, suchas the palms, is abundantly supplied by eccrine sweat glands, but theyare also found in substantial numbers in thin skin.

[0039] In humans, eccrine sweat secretions are complex systemscontaining several electrolytes or ions including sodium (30 to 150mmol), potassium (10 to 40 mmol) and chloride (40 to 110 mmol). It alsocontains non-electrolyte components, such as lactate, urea, glucose,protein, free amino acids, and lipids.

[0040] It has been found that the ions present in eccrine sweat, such assodium (Na+), potassium (K+), nitrate (NO₃−), calcium (Ca₂+) andchloride (Cl−), appear to be released in a pattern linked withovulation. Although variability does exist in the concentration of ionsin eccrine sweat from female to female, the pattern of change in theconcentration of ions in eccrine sweat has been found to repeat duringthe reproductive cycle to permit prediction of ovulation up to 70% to90% accuracy.

[0041]FIGS. 1A to 1C illustrate measurements made of the concentrationsof sodium (Na+) and potassium (K+) ions in eccrine sweat on a dailybasis during the reproductive period of a female human. FIGS. 1A to 1Cshow the concentration of the sodium (Na+) and potassium (K+) ions inmillivolts. FIG. 1D illustrates the concentration of potassium (K+) ionsin the eccrine sweat of the female human measured on a daily basis inmols M.

[0042]FIGS. 1A to 1C also illustrate changes in the conductivity (Cond.)of the eccrine sweat, in microsiemens (uS). It is understood that theconductivity of eccrine sweat will change with the total number of ionspresent. Therefore, measuring conductivity is an indirect method ofmeasuring the total number of ions in the eccrine sweat.

[0043] The adscissa in FIGS. 1A to 1C, as well as the other figuresshowing changes in concentration, shows the cycle days for onereproductive cycle of a female human. For convenience, day 0 on theadscissa corresponds with the day of ovulation, which is also indicatedby the vertical dashed line “0v”. The day of ovulation “0v” wasdetermined by one of the conventional methods, namely detection of theLuteinizing Hormone (LH) which can determine ovulation within about 24hours.

[0044] The values for FIGS. 1A to 1D are indicated by dots and representdaily averages of a number of readings taken over the day, such as 10 to20 in number. This is done to increase accuracy and decrease the effectsof non-hormonal changes in the concentrations of those ions.

[0045]FIG. 1D charts the potassium (K+) ion concentration of eccrinesweat of the female human measured in mols M on a daily basis, whileFIGS. 1A to 1C chart the concentration for these ions in millivolts.This is the case merely because FIGS. 1A to 1C illustrate the value ofthe electrical signal from the sensor for the ion, which is inmillivolts, while FIG. 1D illustrates the converted value of theconcentration in mols M. However, it is understood that the value forthe electrical potential signals in FIGS. 1A to 1C reflect theconcentration of the sodium (Na+) and potassium (K+) ions, and could beconverted to mols M, as was done in FIG. 1D. Furthermore, it isunderstood that the pattern to determine ovulation is based greatly onthe changes in concentration, and therefore the absolute value of theconcentration is not as important as changes in the concentration overtime. The changes in concentration can be determined from both theelectrical potential signals illustrated in FIGS. 1A, 1B and 1C and themolar values illustrated in FIG. 1D.

[0046] As illustrated in FIGS. 1A to 1D, there is a distinct change inthe concentration of both sodium (Na+) and potassium (K+) ions ineccrine sweat at about five days prior to ovulation following aninversion at about seven days before ovulation. Likewise, there is adistinct change in the conductivity, as shown in FIGS. 1A, 1B and 1C atabout five to seven days before ovulation following an inversion atabout seven days before ovulation. This point of an inversion isindicated by Roman numeral I in each of FIGS. 1A to 1D.

[0047] The inversion indicated by reference numeral I in FIGS. 1A to 1Dis generally identified by the distinct change, in this case a decrease,in the concentration, generally in the range of about 40% over theprevious value of the previous day. For FIGS. 1A to 1C, which are inmillivolts, this distinct change in concentration following theinversion is generally shown by a decrease of about 13 millivolts,corresponding to about a 40% decrease in the concentration from theprevious day's value. Therefore, the distinct change is a decrease of40% from the peak or highest value which occurs on or near the day ofinversion.

[0048] As shown in FIGS. 1A and 1C, the inversion is also identified byan earlier surge of about five millivolts, which corresponds to about a25% increase, in the concentration of the sodium (Na+) and potassium(K+) ions. This surge of about 25% in the sodium (Na+) and potassium(K+) ion concentration, followed by the 40% or 13 millivolt decrease,assists in delineating the inversion at point I, which indicatescommencement of the fertile phase.

[0049]FIG. 1D, which illustrates the molar concentration of thepotassium ion (K+) illustrates a similar increase of about 25%, followedby a decrease of 40%. Accordingly, it is apparent that the change in ionconcentrations, whether measured in millivolts or converted to mols M orany other units, can be used to delineate the inversion at point I.

[0050] The method and device according to the present invention monitorsthe output signals from a sensor detecting the concentration of ions, inthe case of FIGS. 1A to 1C potassium (K+) and sodium (Na+) to identify asurge of at least 25% in concentration, followed by a drop of about 40%in concentration. For FIGS. 1A and 1C, which chart changes in thepotential of a sensor for these ions in millivolts, this corresponds toa five millivolt increase and a 13 millivolt decrease, occurring over athree to five day period based on daily averages. Identifying thispattern in the change of concentration of the ions indicatescommencement of the fertile phase in the female human.

[0051] An analysis of FIGS. 1A, 1B and 1C also illustrates the benefitof measuring the change in concentration of more than one ion in eccrinesweat. In particular, as illustrated in FIG. 1B, while there is a clearinversion resulting from a maximum for the potassium (K+) ionconcentration on the sixth day before ovulation, there is a lessdistinct inversion or maximum for the sodium (Na+) ion concentration.Rather, the sodium (Na+) ion concentration experiences an inversion ormaximum followed by a distinct decrease of 40% on the fifth day beforeovulation. Accordingly, by monitoring two ion concentrations, a moreaccurate prediction of ovulation may occur by identifying a distinctchange in the concentration of one of the at least two ions following aninversion which indicates the female human is in the fertile phase.

[0052] As also illustrated in FIGS. 1A and 1B, following the inversion,which in this case is a maximum, as identified by Roman numeral I, theconcentration reaches a maximum or peak at Roman numeral II, which isgenerally about one to two days prior to ovulation. This is followed bya further minimum or nadir shown at Roman numeral III, which generallyoccurs the day before or after ovulation. However, it is understood thatbecause the fertile phase in a female mammal, such as a female human,can begin up to four days prior to ovulation, the nadir at Roman numeralI followed by about a 40% change can best be used to indicatecommencement of the fertile phase.

[0053] With respect to the sodium (Na+) or potassium (K+) ions, aninversion resulting from a maximum or peak has been found to occur atcommencement of the fertile phase, identified by Roman numeral I, asreferred to above. However, it is understood that the maximum is aparticular type of inversion in the direction of change of the ionconcentration. For example, other ions, such as calcium (Ca₂+), havebeen found to reach a minimum rather than a maximum. Accordingly, it isunderstood that an inversion in the concentration can be a minimum(nadir) or maximum (peak), followed by a distinct change which isgenerally about a 40% change.

[0054] Accordingly, FIGS. 1A to 1D illustrate changes in theconcentrations of ions, such as potassium (K+) and sodium (Na+), as wellas changes in the total concentration of all of the ions, as shown bychanges in conductivity (Cond.). As stated above, these changes inconcentration of ions in eccrine sweat can be used to determine that afemale mammal, such as a female human, is in the fertile phase.Furthermore, this determination can be made several days beforeovulation actually occurs, in order to benefit from the entire fertilephase of the female human.

[0055] In particular, FIGS. 1A to 1D illustrate that a distinct change,which in this case is a decrease, in the concentration of one of atleast two ions, such as potassium (K+) and/or sodium (Na+), following aninversion, which in this case is a peak at point I, indicates the femalehuman is in the fertile phase. Moreover, measuring conductivity providesa general indication of the changes in the concentration of the totalnumber of ions in eccrine sweat and has been found to also change insimilar ways. Furthermore, at least for sodium (Na+) and potassium (K+),the inversion followed by a distinct change, can be identified by asurge of about 25%, or about five millivolts, as illustrated in FIGS. 1Ato 1C, followed by a drop of about 40%, or about 13 millivolts. Thissurge followed by a drop defines an inversion, which in this case is apeak or maximum. Identification of this inversion, followed by thedistinct change, in this case the drop of about 40%, indicates thefemale human is in the fertile phase. Other ions, such as chloride,ammonium (NH₄+), calcium (Ca₂+), and nitrate (NO₃−) have been discoveredto behave in similar ways, as described more fully below.

[0056]FIGS. 2A to 2C illustrate changes in the concentration of thechloride (Cl−) ions in the eccrine sweat per day for the reproductivecycle of a number of female humans. As illustrated in FIGS. 2A to 2C,there is generally a surge in the chloride (Cl−) concentration of about25% followed by a decrease of about 40% from the maximum, therebydefining an inversion at point I. This inversion, which for chloride(Cl−) is a maximum, occurs at between three to six days prior toovulation, similar to the sodium (Na+) ion reading shown in FIGS. 1A to1D and can be used to predict ovulation, and therefore commencement ofthe fertile period. Accordingly, monitoring the chloride (Cl−) ion for adistinct change following an inversion can also be used to predictovulation at about three to six days in advance, and therefore determinethe fertile phase of the female human.

[0057] The adscissa in FIGS. 2A to 2C is similar to the adscissa inFIGS. 1A to 1D in that it measures the days of the reproductive cycle ofa female human. Also, the ovulation is shown to occur on day 0 and isalso marked by the vertical dashed line (0v). However, it is noted thatFIGS. 2A and 2B show the Y axis as an inverted millivolt scale. In otherwords, as the millivolt value decreases or becomes more negative, thegraph will increase. This reflects the fact that chloride (Cl−) ions arenegative such that when the chloride concentration increases, there is acorresponding decrease, or greater negative value, in the potential ofthe chloride (Cl−) electrode. Likewise, when there is a decrease in thechloride (Cl−) potential, as occurs following the inversion, there is acorresponding increase, or more positive value, shown at the potentialfor the chloride (Cl−) electrode. Accordingly, FIGS. 2A and 2Billustrate the change in the chloride (Cl−) ion concentration byproviding the outputs in millivolts from the chloride ion, and, for easeof reference, the Y axis has been inverted so that it becomes morenegative when it moves upward on the drawing, reflecting an increase inthe chloride (Cl−) concentration as the potential becomes more negative.This also assists in comparison with the illustrations in FIGS. 1A to 1Cwhich show the millivolt potential for the sodium (Na+) and potassium(K+) electrodes. In FIGS. 1A to 1C, because the ions are positivelycharged sodium (Na+) and potassium (K+) ions, an increase in theconcentration of these ions will be reflected by a more positive valueat the electrode, and therefore an increase in these concentration isillustrated by the graph moving upwards.

[0058] Reference is made to FIG. 2A where at point I, there is aninversion which results after a surge in the chloride (Cl−) ionconcentration of more than five millivolts, which is more than about25%. On the sixth day before ovulation, there is a decrease, but not adistinct decrease, such as about 40%. Rather, there is a large decreasefrom the sixth day to the fifth day of about 40%. Therefore, on dayminus five, following the distinct change of about 40%, there will be anindication that the female human is in the fertile phase. In otherwords, the reading on the sixth day did not indicate a distinct changeso as to conclude that an inversion has occurred.

[0059]FIG. 2B also illustrates an inversion at day minus five. Theinversion is preceded by an increase of at least 25%, or in this case,more than five millivolts, and followed by a distinct change or decreaseof at least 40% or in this case, 13 millivolts. It is noted that at daythree before ovulation, there is also a similar inversion, but at a muchlower concentration. This second inversion at day three before ovulationwill be ignored by the present invention at least because an indicationwould already have been made that the female human is in the fertilephase as of day five before ovulation.

[0060] It is noted that FIGS. 2A and 2B also show a portion marked byreference numeral II where the chloride (Cl−) ion concentration reachesa minimum or nadir, as is also shown in FIGS. 1A to 1D. This minimum isbelieved to coincide with a rise in serum total estrogen 24 to 48 hoursprior to ovulation. While one advantage of the present invention is thatit would have determined at the inversion I that the female human is inthe fertile phase, the portion II could be used to confirm that thefemale human is in the fertile phase, or even to determine that thefemale human is now in the fertile status of ovulation. This can befurther confirmed by the further increase shown at point III near theday of ovulation “0v”. The portion II is not used to determine thefertile phase in general because the inversion I can determine thefertile phase much earlier.

[0061]FIG. 2C is similar to FIGS. 2A and 2B in that it shows thechloride concentration by means of showing the change in the millivoltvoltage at the chloride (Cl−) electrode. Likewise, FIG. 2C shows a surgeor increase in the chloride (Cl−) concentration between day eight to dayseven prior to ovulation which is followed by a distinct change betweenday seven and day five causing an inversion at point I at day sevenbefore ovulation. FIG. 2C also shows a decrease in chloride (Cl−)concentration one day before ovulation, marked by point II. Finally,FIG. 2C, as with FIGS. 2A and 2B, show a further increase inconcentration at the date of ovulation marked by point III.

[0062] In addition, FIG. 2C shows an early inversion or peak at day 12before ovulation, marked by point IV. This point IV is a false inversionpoint which would not be considered by the system as the inversion whichindicates commencement of the fertile phase at least because it occurredtoo early in the reproductive cycle of the female human. False inversionpoint IV can be easily discounted by the system estimating the averagereproductive cycle of the female human, and subtracting 19 days prior tothe expected menstruation and ignoring all data before this time period.The 19 day period arises because the Luteal period is about 14 days fromovulation to menstruation. Accordingly, false peaks, such as that shownat point IV, would be discounted.

[0063]FIGS. 3A and 3B illustrate ratiometric measurements with respectto one ion, in the case of FIGS. 3A and 3B, being the sodium (Na+) ion.FIG. 3A shows a ratiometric measurement of ammonium (NH₄+) with respectto sodium (Na+), and, indicates an inversion at day two beforeovulation. This corresponds with measurements of increases in ammonia(NH₄+) which occur at about two to three days before ovulation.

[0064]FIG. 3B illustrates a ratiometric measurement of chloride (Cl−) tosodium (Na+). As can be seen from FIG. 3B, this graph is relativelyflat, which would be expected because chloride (Cl−) is the counterionfor sodium (Na+). Accordingly, a ratiometric measurement of chloride(Cl−) with respect to sodium would not be of great assistance inidentifying commencement of the fertile phase in the female human.

[0065]FIG. 3C is shown merely for comprehensiveness and shows the ratioof sodium (Na+) to sodium (Na+), which is one, as would be expected.

[0066]FIG. 3D shows a ratio of potassium (K+) with respect to sodium(Na+) and, as is the case with FIG. 3B which shows a ratio of chloride(Cl−) with respect to sodium (Na+), does not show any great changesbefore ovulation. This would also be consistent with sodium andpotassium experiencing similar changes in concentration during thereproductive cycle, as illustrated for instance in FIGS. 1A to 1C.

[0067]FIG. 3E illustrates a ratiometric measurement of calcium (Ca₂+)with respect to sodium (Na+). This ratiometric measurement shows adecrease in the relative concentration of the calcium (Ca₂+) ion withrespect to the sodium (Na+) ion about two days before ovulation.

[0068] It is apparent from FIGS. 3A to 3E that ratiometric measurementsof ions, such as ammonium (NH₄+) and calcium (Ca₂+) with respect tosodium (Na+), can be used to identify an inversion and predict ovulationabout two days in advance. By using a ratiometric measurement,fluctuations in total eccrine sweat can be removed, thereby providing amore accurate prediction of ovulation, but generally only about two daysin advance of ovulation.

[0069]FIGS. 3B and 3D illustrate that ratiometric measurements ofchloride (Cl−) and potassium (Ka+) with respect to sodium are not veryuseful to predict ovulation. This would be expected as each of chloride(Cl−), sodium (Na+) and potassium (K+) vary about the same during thereproductive cycle, as illustrated in FIGS. 1A to 1D and 2A to 2C.

[0070] While not shown in the drawings, corresponding tests with respectto other ions, such as nitrate (NO₃−), have shown that nitrate (NO₃−)reacts in a similar manner to ammonium (NH₄+). Accordingly, FIG. 3A,which illustrates the ratiometric measurements of ammonium (NH₄+) withrespect to sodium (Na+) would be similar to the ratiometric measurementsof nitrate (NO₃−) with respect to sodium (Na+).

[0071] By comparing FIG. 3A (for ammonium (NH₄+)) and FIG. 3E (forcalcium (Ca₂+)), it is apparent that the concentrations for these twoions move in opposite directions during the relevant period prior toovulation. In particular, ammonium (NH₄+) with respect to sodium (Na+)appears to peak with respect to sodium (Na+) two days before ovulationwhile calcium (Ca₂+) appears to have a nadir with respect to sodium twodays before ovulation.

[0072] Accordingly, rather than taking a ratiometric measurement of oneof these ions (Ca₂+ or NH₄+) with respect to a fairly stable ion, suchas sodium (Na+) or chloride (Cl−), in order to more accurately identifychanges in the concentration of the ions in eccrine sweat, the presentinvention also provides for the ability to take a ratio of two ionswhich move in opposite directions, such as ammonium (NH₄+) and calcium(Ca₂+) This is illustrated in FIG. 4 which is a ratiometric measurementof ammonium with respect to calcium (NH₄+/Ca₂+). FIG. 4 illustrates aninversion, shown by point I, occurring at about three days beforeovulation. This is then followed by a distinct change, in this case anincrease in the ratiometric value at two days before ovulation asindicated by point II. Accordingly, a ratiometric measurement betweenammonium (NH₄+) and calcium (Ca₂+) can also be used to identify thefertile phase by predicting ovulation about two to three days inadvance. Furthermore, using a ratiometric measurement of ions which movein opposite directions, such as ammonium (NH₄+) and calcium (Ca₂+), canprovide a more pronounced change in the ratiometric value of more than50% and about 80%, thereby further delineating the inversion I andproviding a more accurate measurement to be made.

[0073]FIG. 5 shows a drawing, similar to that shown for FIG. 3A, of aratiometric value for ammonium (NH₄+) with respect to sodium (Na+).However, FIG. 5 is more accurate and shows an inversion occurring atabout four days before ovulation. Accordingly, FIG. 5 suggests that insome cases, a ratiometric measurement of ammonium (NH₄+) with respect tosodium (Na+) may show an inversion with a nadir of ammonium (NH₄+) withrespect to sodium (Na+) at day four before ovulation, followed by adistinct rise at day three before ovulation. In such cases, the presentinvention will indicate that the female human is in the fertile phase atday three before ovulation and provide an earlier measurement than thepeak at day two before ovulation. Accordingly, a ratiometric measurementof ammonium (NH₄+) with respect to sodium (Na+) can predict ovulation atleast two days in advance, and in some cases three to four days inadvance. FIG. 5 also illustrates that with respect to ratiometricmeasurements, an inversion, either being a maximum or a minimum, mayoccur which would be expected because the relative values of ions arebeing measured and can result in more fluctuation.

[0074]FIG. 6 illustrates a ratiometric measurement of sodium (Na+) withrespect to calcium (Ca₂+). FIG. 6 is similar to FIG. 3E, except thatFIG. 6 shows the ratio of sodium (Na+) with respect to calcium (Ca₂+),and therefore is the inversion of the graph shown in FIG. 3E. This iswhy FIG. 6 shows a peak while FIG. 3E shows a nadir two days beforeovulation.

[0075] In another method, rather than determining the concentration oftwo ions using two ion electrodes and one reference electrode, and thendetermining the ratio of their concentration, the determination may besimplified by eliminating the reference electrode and simply measuringthe potential difference between two sensing electrodes. In this case,the relative ratiometric change in the ion concentrations is detected bythe potential difference between the two sensors alone. An example isshown in FIG. 7 for a sodium (Na+) electrode with respect to a calcium(Ca₂+) electrode, and in FIG. 8 for a chloride (Cl−) electrode withrespect to a calcium (Ca₂+) electrode. To explain by example, in FIG. 7,as the calcium (Ca₂+) concentration in the sweat drops with respect tosodium (Na+), the calcium (Ca₂+) electrode becomes more negative, andthus the potential difference between the two electrodes increases. Ifthe sodium (Na+) concentration drops with respect to calcium (Ca₂+),electrode potential will decrease.

[0076] As can be seen from FIGS. 7 and 8, a peak can be seen in thecurves about one day prior to ovulation in a manner consistent with theratiometric measurements shown in FIGS. 5 and 6. It should be noted thatthis method is not as accurate as with the true ratiometric method usedin FIGS. 5 and 6, since the changes seen indicate only relative changesin the concentrations of the ions. As well, a divalent ion sensorpotential change will only be half that of a monovalent ion for the sameconcentration change. However, where the ratio changes of the ions inquestion is large and obvious this method is advantageous in thesimplicity it affords to the reduced sensor arrangement, and inparticular, to the elimination of the reference electrode.

[0077]FIG. 9 illustrates a schematic diagram of a circuit, showngenerally by reference numeral 100, to sense one or two ions, accordingto one preferred embodiment of the present invention. As shown in FIG.9, the sensor 100 comprises an ammonium (NH₄+) electrode 110 and asecond electrode, which in FIG. 9 is shown as being either a calcium(Ca₂+) or chloride (Cl−) electrode 120. Accordingly, the sensor 100illustrated in FIG. 9 can be used to sense the relative change inconcentration of ammonium (NH₄+) with respect to either calcium (Ca₂+)or chloride (Cl−) and provide an output to an analog to digital (A/D)converter at output 140 reflecting a potential difference of theseelectrodes.

[0078] Accordingly, the output 140 for sensor 100 illustrated in FIG. 9could contain output signals corresponding to a ratiometric measurementof ammonium (NH₄+) with respect to calcium (Ca₂+) when the secondelectrode 120 is a calcium (Ca₂+) electrode. Therefore, the outputsignals for such a sensor 100 would be similar to that shown in FIGS. 7or 8 and would be unit independent as it is a ratiometric measurement ofrelative ion concentration. Likewise, the output 140 for sensor 100illustrated in FIG. 9 could contain output signals corresponding to arelative ratiometric measurement of ammonium (NH₄+) with respect tochloride (Cl−) when the second electrode 120 is a chloride (Cl−)electrode.

[0079] As also illustrated in FIG. 9, the sensor 100, in one preferredembodiment, comprises an operational amplifier 130, which in thisembodiment is Model MIC7111, and provides about ten times amplificationof the relative potential between the first electrode 110 and the secondelectrode 120. The sensor 100 in this preferred embodiment alsocomprises resistors R1, R2, R3, R5, R6 and an input voltage Vdd toprovide amplification and stability for the sensor 100.

[0080] The output electrode 140 is shown in FIG. 9 as being connected toan A/D converter circuit (not shown). It is understood that the A/Dconverter circuit (not shown) could be a separate circuit or could formpart of a processor, as shown in FIG. 11 by reference numeral 400.

[0081] The first electrode 110 and the second electrode 120 could be anyknown type of electrode for measuring ammonium (NH₄+), calcium (Ca₂+),chloride (Cl−), or any of the other ions referred to above, such assodium (Na+), potassium (K+) and nitrate (NO₃−). The electrodes 110, 120could also be a conductivity sensor to sense conductivity (Cond.), asdescribed above with respect to FIGS. 1A to 1C. In this case, the sensor100 would incorporate an electronic voltage circuit (not shown), as isknown in the art, to sense the conductivity (Cond.) between theelectrodes. FIG. 10A to 10C illustrate representations of the electrodeswhich could be used for the first electrode 110 and the second electrode120. Electrode 120 could also be a standard reference electrode if thecircuit is used to measure the concentration of one ion only with thefirst electrode 110 being the appropriate ion sensor. For instance, themeasurements of the sodium (Na+), chloride (Cl−) and potassium (K+) ionsas illustrated in FIGS. 1A to 1D and 2A to 2C were obtained by havingthe first electrode 110 being an appropriate electrode to sense sodium(Na+), chloride (Cl−) and potassium (K+), respectively, and the secondelectrode 120 being a standard reference electrode. In a preferredembodiment, where relative changes in concentration are being measured,the first electrode 110 is selected to sense the concentration of afirst ion, such as ammonium (NH₄+), and the second electrode 120 isselected to sense a second ion, such as calcium (Ca₂+). Othercombinations of electrodes 110, 120 to sense concentrations of thedifferent ions described above could be used. This avoids the need for areference electrode because both electrodes would be measuring thechanges in concentrations of a particular ion, and then, a relativeratio could be obtained.

[0082]FIG. 10A shows an ammonium ion-selective electrode, showngenerally by reference numeral 200, as is known in the art. The ammoniumion-selective electrode 200 comprises a silver/silver chloride-coateddisk electrode 202 in electrical contact with a 0.01M solution ofammonium chloride 220 which in turn is in electrical contact with anammonium ionophoric membrane 210. The ammonium ion-selective electrode200 will provide an output potential at output 325 which is electricallyconnected to the disk 202. This output potential will be an electricaloutput signal with respect to a standard reference electrode whichcorresponds to the ammonium (NH₄+) concentration in the eccrine sweat incontact with the ammonium ionophoric membrane 210.

[0083]FIG. 10C shows a calcium ion-selective electrode 400. The calciumion-selective electrode 400 is similar to the ammonium ion-selectiveelectrode 200 in that it has a silver/silver chloride-coated diskelectrode 402, a 0.01M solution of calcium chloride (CaCl₂) 420 and acalcium ionophoric membrane 410. The calcium ion-selective electrode 400can sense the concentration of calcium (Ca₂+) ion in the eccrine sweatand produce an output potential at output 325 with respect to a standardreference electrode which is electrically connected to the diskelectrode 402. The output potential will be an electrical output signalcorresponding to the concentration of the calcium (Ca₂+) ion in eccrinesweat.

[0084]FIG. 10B shows a chloride ion-selective electrode, shown generallyby reference numeral 300. Unlike the ammonium and calcium ion-selectiveelectrodes 200, 400, the chloride ion-selective electrode 300 has a solesilver/silver chloride-coated disk electrode 350. The disk electrode 350will produce an output potential with respect to a standard referenceelectrode which can be sent to the output 325. The output potential willbe an electrical output signal which corresponds to the concentration ofchloride (Cl−) ions in the eccrine sweat.

[0085] The electrodes 200, 300 and 400 shown in FIGS. 10A, 10B and 10Ccan also be used individually in order to sense changes in concentrationof a single ion, such as ammonium (NH₄+), chloride (Cl−) or calcium(Ca₂+) with respect to a standard reference electrode. For instance, thesilver/silver chloride-coated disk electrode 350 could be used to sensethe chloride (Cl−) ion concentration which can be used to determine thefertile phase as described above with respect to FIGS. 2A to 2C.Similarly, known electrodes and sensors to sense other characteristicsof eccrine sweat, such as sodium (Na+), nitrate (NO₃−) and potassium(K+) ion concentrations and conductivity could also be used. Inaddition, the electrodes 200, 300 and 400, as well as similar knownelectrodes and sensors to sense other characteristics of eccrine sweat,such as sodium (Na+), nitrate (NO₃−) and potassium (K+), could be usedconnected to the first electrode 110 or second electrode 120 to providechanges in relative concentrations of two ions. As discussed above,because the present invention monitors changes in concentrations, ratherthan absolute concentrations, measurements provided, such as by therelative potential of two electrodes, is sufficient to operate theinvention.

[0086]FIG. 11 shows a schematic diagram of a sensor, shown generally byreference numeral 500, according to a further embodiment of the presentinvention.

[0087] The sensor 500 is similar to the sensor 100 in that it comprisesan amplifier 130, which is model MIC7111 and resistors R1, R2, R3, R5and R6 to complete the circuit. However, FIG. 11 differs in that it hasthree electrodes, namely a first sensor electrode 501, a second sensorelectrode 502 and a reference electrode 503. The sensor electrodes 501and 502 can be any type of electrode to sense the concentration of anion in the eccrine sweat, such as calcium (Ca₂+), chloride (Cl−),ammonium (NH₄+), shown in FIGS. 10A to 10C, or any other ions to senseanother ion or conductivity. Likewise, reference 503 can be a standardreference electrode, or alternatively, can provide a potentialindicative of the concentration of a reference ion, such as chloride(Cl−), sodium (Na+) or potassium (K+) in the eccrine sweat to provideratiometric measurements, as illustrated above in FIGS. 3A to 3E, 4, 5and 6.

[0088] Sensor 500 also comprises a switch 504 which is controlled by themicrocomputer 550 to switch between taking measurements of the sensorelectrode 501 or the sensor electrode 502. In other words, themicroprocessor 550 can take two separate ratiometric measurements,namely a first ratiometric measurement of the potential of the sensor501 with respect to the reference 503, and a second ratiometricmeasurement of the potential of the sensor 501 with respect to thepotential of the reference 503. The microprocessor 550 can then comparethese two separate ratiometric measurements to provide a further, moreaccurate ratiometric measurement.

[0089] In a preferred embodiment, the sensor 501 is an ammonium (NH₄+)electrode, such as electrode 200 shown in FIG. 10A, the sensor 502 is acalcium (Ca₂+) electrode, such as the electrode 400 shown in FIG. 10Cand the reference electrode 503 is a chloride (Cl−) electrode 300 asshown in FIG. 10B. In this way, ratiometric measurements of ammonium(NH₄+) with respect to a reference ion, such as chloride (Cl−), and thencalcium (Ca₂+) with respect to the same reference ion, can be obtainedand transferred to the microprocessor 550. The microprocessor 550 willthen compare the ratiometric measurements of ammonium (NH₄+) withrespect to chloride (Cl−) and also the ratiometric measurement ofcalcium (Ca₂+) with respect to chloride (Cl−) to provide a ratiometricmeasurement of ammonium (NH₄+) with respect to calcium (Ca₂+). However,because this final ratiometric measurement of ammonium (NH₄+) withrespect to calcium (Ca₂+) was initially with respect to a reference ion,such as chloride (Cl−), the effects with respect to the volume ofeccrine sweat, as well as accumulation of ions on the skin can beremoved. Accordingly, sensor 500 can be used to provide a more accuratemeasurement of the relative concentration of ammonium (NH₄+) withrespect to calcium (Ca₂+). In addition to chloride (Cl−), sodium (Na+)and potassium (K+) could also be used as reference ions.

[0090] As shown in FIG. 11, the sensor 500 shows the switch 504 beingcontrolled by one of the output ports 552 b. The second output port 552a provides power to the sensor circuit as required. The integratedcircuit 560 receives the relative potential signal from the amplifier130, and in this preferred embodiment, comprises an analog to digitalconverter, to convert the analog signal from the amplifier 130 to adigital signal which can be processed by the microprocessor 550.Input/output ports 552 c, 552 d, 552 e and 552 f are connected to aclock and integrated circuit 560 to assist in running a sensor 500, asis known in the art.

[0091] The microprocessor unit 550 also generally contains memory so asto store the various measurements made during the day. In this way, adaily average based on a number of readings can be obtained.Furthermore, the microprocessor 550 to count out periods of time, suchas 30 or 60 minute intervals, so that readings can be taken throughoutthe day and averaged. Preferably, the readings are taken at the sametime each day so that any changes in the concentration of ions ineccrine sweat due to daily variations, either to diet or activity, willnot adversely affect the results.

[0092] In a preferred embodiment, the microprocessor unit 550 causes thesensor 100, 500 to sense the concentration of at least one of the ionsat least six times per day. In this way, the processor can accumulate atleast six readings per day, and preferably more, and use these sixreadings in a statistical analysis to provide a daily average of theconcentration. The statistical analysis may include eliminating one ormore of the readings which are considered spurious and/or fitting thereadings to a gaussian distribution in order to more clearly determinethe average. In more sophisticated embodiments, readings taken at thesame time during the day will be given more weight in order to accountfor and eliminate differences which may arise in the concentration ofthe ions during a day.

[0093] The daily averages can be stored in any type of known storagedevice contained within the device 500. In a more advanced system, thereadings can be transmitted to a remote location, such as by wirelesstransmission and/or non-wireless transmission, and then stored andanalyzed at the remote location, such as a central computing ormonitoring laboratory.

[0094] The processor 550 also preferably contains some random accessmemory (RAM ), shown generally by reference numeral 580, which can storevarious information, and in particular readings and or results ofprevious reproductive cycles. Accordingly, the daily readings can bestored in the RAM 580 and/or downloaded, either through a serialconnection or a wireless connection, for further analysis and/or recordkeeping by a remotely located computer or the processor 550. The resultsof previous reproductive cycles can also be used to estimate theduration of the reproductive cycle for each female, as described above.This provides an estimate of the commencement of the reproductive cycle,and thereby permits the processor 550 to discount or ignore earlierspurious readings, as described above for instance with respect to FIG.2C.

[0095]FIG. 12 is a diagram showing the device 700 according to oneembodiment of the present invention. As shown in FIG. 12, the devicecomprises a display 710 for displaying, amongst other things, thefertility status of the female. Initially, the display 710 will indicatethat the female is not fertile. Once the determination is made that thefemale is in the fertile phase, the display 710 indicates that thefemale is fertile, followed by an indication again that the female isagain not fertile after one day following ovulation. Optionally, thedisplay 710 may also display “0v” indicating that the device 700 hasdetermined that the female is ovulating.

[0096] As also shown in FIG. 12, the device 700 comprises a strap 720such that the device 700 can be strapped to the surface of the skin ofthe user for extended periods of time. This facilitates taking readingsover a longer period of time, such as several hours during the dayand/or night, without adversely impacting on the mobility of the user.Furthermore, in a preferred embodiment, the device 700 comprises a clockwhich displays the time over the period of the day so that the device700 can appear as a regular wrist watch. Also, because the device 700 isattached to the surface of the skin of the user for extended periods oftime and comprises a clock, the device 700 can automatically andrepeatedly take readings in 30 or 60 minute intervals, or other timeintervals, as described above, throughout the day without the user evenbeing aware that the readings are being taken.

[0097] In a further preferred embodiment, the device 700 is manufacturedfrom a plastic material and has on the side opposite the display 710 aflat plastic surface which promotes sweating when placed against theskin of the user. In a further preferred embodiment, the device 700comprises a flange around an area in order to pool the eccrine sweat ata location near the location of the sensors 100, 500. This facilitatessweating and pooling of the eccrine sweat near the sensors 100, 500 sothat more accurate readings can be obtained.

[0098] It is understood that both ionophoric and solid state sensors, aswell as other types of sensors, could be used to determine theconcentration of ions in eccrine sweat. In a preferred embodiment, solidstate sensors, in particular when chloride (Cl−) ions are being sensed,have been found to be very stable.

[0099] It is understood that the present invention has been defined withrespect to use by a woman, which has also been referred to as a femalehuman. However, the present invention is not limited to use by femalehumans. Rather, the present invention has applicability with othermammals which excrete eccrine sweat and can be used in the veterinarianfield. Moreover, the present invention has been found to be useful withrespect to pigs, horses and bovine. However, it is understood that someof the time periods and indicators may change for other mammals.

[0100] It will be understood that, although various features of theinvention have been described with respect to one or another of theembodiments of the invention, the various features and embodiments ofthe invention may be combined or used in conjunction with other featuresand embodiments of the invention as described and illustrated herein.

[0101] Although this disclosure has described and illustrated certainpreferred embodiments of the invention, it is to be understood that theinvention is not restricted to these particular embodiments. Rather, theinvention includes all embodiments which are functional, electrical ormechanical equivalents of the specific embodiments and features thathave been described and illustrated herein.

The embodiments of the invention in which an exclusive property orprivilege is claimed are defined as follows:
 1. A device for determininga fertile phase of a female human comprising: (a) a sensor for sensingconcentrations of at least two ions in the eccrine sweat of the femaleand generating output signals indicative of concentrations of the atleast two ions in the eccrine sweat; (b) a processor for controlling thesensor to sense the concentrations of at least two ions in the eccrinesweat substantially simultaneously and at least on a daily basis; andwherein the processor monitors the output signals from the sensor toidentify a distinct change in the concentration of one of the at leasttwo ions following an inversion which indicates the female human is inthe fertile phase.
 2. A device as claimed in claim 1, wherein the atleast two ions sensed in the eccrine sweat are selected from the groupconsisting of sodium (Na+), potassium (K+), ammonium (NH₄+), calcium(Ca₂+), chloride (Cl−) and nitrate (NO₃−) of the eccrine sweat.
 3. Thedevice as claimed in claim 1, wherein the at least two ions comprise afirst ion and a second ion; and the processor monitors a ratio of theconcentration of the first ion to the second ion to identify a distinctchange in the concentration of the at least two ions following aninversion indicating the female human is in the fertile phase.
 4. Thedevice as claimed in claim 3, wherein the first ion is selected from thegroup consisting of potassium (K+), nitrate (NO₃−), ammonium (NH₄+) andcalcium (Ca₂+) and, a second ion is selected from the group consistingof sodium (Na+) and chloride (Cl−).
 5. The device as claimed in claim 3,wherein the first ion is selected from the group consisting of potassium(K+), nitrate (NO₃−) and ammonium (NH₄+), and the second ion is selectedfrom the group consisting of calcium (Ca₂+).
 6. The device as claimed inclaim 3, wherein the first ion is ammonium (NH₄+) and the second ion iscalcium (Ca₂+).
 7. The device as claimed in claim 5, wherein the atleast two ions comprise a third ion selected from the group consisted ofsodium (Na+) and chloride (Cl−); and wherein the processor monitors afirst preliminary ratio of the concentration of the first ion withrespect to the third ion, and, a second preliminary ratio of theconcentration of the second ion with respect to the third ion, and, theprocessor then monitors a ratio of the first preliminary ratio to thesecond preliminary ratio to identify a distinct change in theconcentration of the at least two ions following an inversion indicatingcommencement of a fertile phase.
 8. A device as claimed in claim 3,wherein the device further comprises a display for displaying charactersindicating the female human is in the fertile phase.
 9. A device asclaimed in claim 3, further comprising a fastener for fastening thedevice to the female subject such that the sensor contacts the skin ofthe female at least six hours each day; and wherein the processorcontrols the sensor to sense the concentration of the at least two ionsbetween eight to eighteen times each day to monitor a daily average ofthe concentrations.
 10. A device as claimed in claim 3, wherein thefertile state of ovulation is predicted to occur within six daysfollowing the inversion.
 11. A device for determining the fertilitystatus of a female mammal comprising: (a) a sensing means for sensing atleast one ion selected from the group consisting of potassium (K+),ammonium (NH₄+), calcium (Ca₂+), chloride (Cl−), nitrate (NO₃) andsodium (Na+), in the eccrine sweat of the female mammal and generatingoutput signals indicative of the concentration of ions in the eccrinesweat; (b) processor means for controlling the sensing means to sensethe at least one ion in the eccrine sweat at least on a daily basis; andwherein the processor means monitors the output signals stored in thestorage means to identify a distinct change in a concentration of one ofthe ions following an inversion which indicates the female mammal is inthe fertile phase.
 12. A device as claimed in claim 11, wherein thefemale mammal is a female human and the distinct change is a change ofat least 40% following the inversion.
 13. A device as claimed in claim11, wherein the device further comprises a display means for indicatingthe female mammal is in the fertile phase.
 14. A device as claimed inclaim 11, wherein the sensing means utilizes a solid state sensor. 15.The device defined in claim 11, wherein the female mammal is a femalehuman and the processor causes the sensing means to sense theconcentration of the at least one ion at least six readings per day andstatistically analyzes the at least six readings to provide an averageof the concentration for the day; and wherein the processor meansmonitors the average of the concentration of one of the ions to identifya distinct change in the concentration of one of the ions following aninversion which indicates the female human is in the fertile phase. 16.The device as defined in claim 16, further comprising: storage means forstoring information regarding previous reproductive cycles of thefemale; and wherein the processor utilizes the information to predict anexpected duration of the reproductive cycle and disregard output signalsobtained for an initial portion of a reproductive cycle of the femalemammal immediately following menstruation.
 17. The device as defined inclaim 16, wherein the initial portion which is disregarded is prior to19 days before an estimated end of the reproductive cycle.
 18. Thedevice as claimed in claim 17, wherein the at least two ions comprise afirst ion and a second ion; and the processor monitors a ratio of theconcentration of the first ion to the second ion to identify a distinctchange in the concentration of the one of the at least two ionsfollowing an inversion which indicates the female human is in thefertile phase.
 19. The device as claimed in claim 18, wherein the firstion is selected from the group consisting of potassium (K+), nitrate(NO₃−), ammonium (NH₄+) and calcium (Ca₂+), and, a second ion isselected from the group consisting of sodium (Na+) and chloride (Cl−).20. A device as claimed in claim 11, wherein the female mammal is afemale human and ovulation is ascertained to occur within six daysfollowing the inversion.
 21. A device as claimed in claim 1, wherein thesensor comprises a conductivity sensor to sense conductivity of theeccrine sweat; wherein the sensor senses the concentration of the atleast two ions by sensing the conductivity of the eccrine sweat; andwherein the processor monitors the output signals from the sensorindicating conductivity of the eccrine sweat to identify a distinctchange in the concentration of one of the at least two ions following aninversion which indicates the female human is in the fertile phase. 22.A device as claimed in claim 2, wherein to identify a distinct change inthe concentration of one of the least two ions following an inversion,the processor monitors the output signals to identify a surge of 25%followed by a drop of 40% in the concentration of one of the at leasttwo ions.
 23. A method for determining a fertile phase of a female humancomprising the steps of: (a) sensing concentration of at least two ionsin eccrine sweat of the female human substantially simultaneously and atleast on a daily basis; (b) generating output signals indicative ofconcentrations of the at least two ions in the eccrine sweat; (c)monitoring the output signals to identify a distinct change in theconcentration of one of the at least two ions following an inversionwhich indicates the female human is in the fertile phase.
 24. The methodas defined in claim 23, wherein steps (a) and (b) further comprise thesteps of: (i) sensing concentrations of the at least two ions by sensingconductivity of the eccrine sweat; and (ii) generating output signalsindicative of concentrations of the at least two ions in the eccrinesweat by generating output signals indicating conductivity of theeccrine sweat.
 25. The method as defined in claim 23, wherein step (c)further comprises the step of: (i) monitoring the output signals toidentify a surge of at least 25% followed by a drop of at least 40% inthe concentration of one of the at least two ions indicating the femalehuman is in the fertile phase.
 26. The method as defined in claim 23,wherein the at least two ions sensed in the eccrine sweat are selectedfrom the group consisting of sodium (Na+), potassium (K+), ammonium(NH₄+), calcium (Ca₂+), chloride (Cl−) and nitrate (NO₃−) of the eccrinesweat pH.
 27. The method as defined in claim 23, wherein the at leasttwo ions comprise a first ion and a second ion and wherein step (c)comprises the step of: (i) monitoring a ratio of the concentration ofthe first ion to the second ion to identify a distinct change in theconcentration of one of the at least two ions following an inversionindicating the female human is in the fertile phase.
 28. The method asdefined in claim 27, wherein the first ion is selected from the groupconsisting of potassium (K+), nitrate (NO₃−), ammonium (NH₄+) andcalcium (Ca₂+), and, a second ion is selected from the group consistingof sodium (Na+) and chloride (Cl−).
 29. The method as defined in claim27, wherein the first ion is selected from the group consisting ofnitrate (NO₃−) and ammonium (NH₄+), and the second ion is selected fromthe group consisting of calcium (Ca₂+).
 30. The method as defined inclaim 23 comprising the further steps of: sensing concentrations of theleast two ions substantially simultaneously and at least six times aday; generating output signals indicative of concentrations of the atleast two ions in the eccrine sweat; processing the output signals toprovide a daily average of the at least two ions; monitoring the dailyaverages of the output signals to identify a distinct change in theconcentration of one of the at least two ions following an inversionwhich indicates the female human is in the fertile phase.
 31. The methodas defined in claim 23 further comprising the steps of: storinginformation regarding previous reproductive cycles of the female;predicting, based on the stored information regarding previousreproductive cycles of the female, an expected duration of thereproductive cycle and disregarding output signals prior to 19 daysbefore an estimated end of the expected duration of the reproductivecycle.